Changes of miRNA expression in obstructive and neurogenic bladder dysfunction. bladder dysfunction

Lower urinary tract dysfunction (LUTD) has multiple causes including bladder outlet obstruction (BOO) as a result of benign prostatic hyperplasia (BPH) and neurological diseases including spinal cord injury (SCI). The consequences of both BOO-induced (BLUTD) and neurogenic LUTD (NLUTD), either the low compliance high pressure bladder or the acontractile bladder, are believed to share some pathogenetic mechanisms. Recently we have established miRNA and mRNA expression profiles of several urodynamically defined states of BLUTD. In this follow-up project we propose to extend these studies, undertaking a comparative miRNA and mRNA profiling of BLUTD and NLUTD, and investigate the dynamic alteration of miRNA expression in different functional manifestations of disease. Monitoring the reversal of changes in miRNA expression after relief of obstruction and restoration of normal bladder function will help delineate the key BOO-induced miRNAs with regulatory potential. Similarly, the dynamics of miRNA alteration, observed in SCI patients should reveal the role of miRNA in gene expression regulation during neurogenic-induced organ remodelling. By uncovering the molecular similarities and differences between BLUTD and NLUTD, we will elucidate some of the causative factors in the development of these disorders and highlight the impact of myogenic and neurogenic components postulated to be involved.